title: Regulation of tight junctions by sex hormones in normal human endometrial epithelial cells and uterus cancer cell line Sawano.
abstract: The number of patients with uterine endometrial carcinoma, the cause of which involves sex hormones, has recently been growing rapidly because of increases in life expectancy and obesity. Tight junction proteins claudin-3 and -4 are receptors of Clostridium perfringens enterotoxin (CPE) and increase during endometrial carcinogenesis. In the present study of normal human endometrial epithelial (HEE) cells and the uterus cancer cell line Sawano, we investigate changes in the expression of tight junction proteins including claudin-3 and -4, the fence and barrier functions of the tight junction and the cytotoxic effects of CPE by sex hormones. In primary cultured HEE cells, treatment with progesterone (P4) but not estradiol (E2), induced claudin-1, -3, -4 and -7 and occludin, together with the downregulation of the barrier function but not the fence function. In Sawano cells, claudin-3 and -4 were upregulated by E2 but not by P4, together with a disruption of both the barrier and fence function. In primary cultured HEE cells, claudin-3 and -4 were localized at the apicalmost regions (tight junction areas) and no cytotoxicity of CPE was observed. In Sawano cells, claudin-3 and -4 were found not only in the apicalmost regions but also at the basolateral membrane and the cytotoxicity of CPE was enhanced by E2. Thus, tight junctions are physiological regulated by sex hormones in normal HEE cells during the menstrual cycle suggesting that safer and more effective therapeutic methods targeting claudins in uterine cancer can be developed.
authors.affiliation: Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Someya
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Marie
authors.initials: M
authors.lastname: Ogawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nomura
authors.forename: Akira
authors.initials: A
authors.lastname: Takasawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Murata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004717:Endometrium / Q000166:cytology; D004768:Enterotoxins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011374:Progesterone / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*; D015854:Up-Regulation; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism
chemical_list: D057167:Claudins; D004768:Enterotoxins; C035598:enterotoxin, Clostridium; D011374:Progesterone; D004958:Estradiol